2.1. Steric Relationship and Drug Action
Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of plane-polarized light. In describing an optically active compound, the prefixes D and L or R and S are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes d and l or (+) and (-) are employed to designate the sign of rotation of plane-polarized light by the compound, with (-) or l meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these compounds, called stereoisomers, are identical except that they are mirror images of one another. A specific stereoisomer may also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric or racemic mixture.
Stereochemical purity is of importance in the field of pharmaceuticals, where 12 of the 20 most prescribed drugs exhibit chirality. A case in point is provided by the L-form of the .beta.-adrenergic blocking agent, propranolol, which is known to be 100 times more potent than the D-enantiomer.
Furthermore, optical purity is important since certain isomers may actually be deleterious rather than simply inert. For example, it has been suggested that the D-enantiomer of thalidomide was a safe and effective sedative when prescribed for the control of morning sickness during pregnancy, while the corresponding L-enantiomer has been thought to be a potent teratogen.
The active compound of the present invention is the S(-) isomer of the compound nitrendipine, which is described in U.S. Pat. No. 3,799,934. Chemically, this compound is the S(-) isomer of 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid ethyl methyl ester or ethyl 1,4-dihydro-5-(acetoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-3-pyrindine carboxylate. This isomer will hereinafter be referred to as S(-) nitrendipine. The terms "S(-) nitrendipine" and "S(-) isomer of nitrendipine" as used herein includes substantially optically pure S(-) nitrendipine as well as optically pure S(-) nitrendipine. Further, these terms as used herein refers to any biologically acceptable form thereof, such as a salt or ester of this compound.